Compliant Biocompatible Device and Method of Manufacture

ABSTRACT

As detailed herein, a biocompatible apparatus comprises a porous material comprising ceramic nanotubes bound together with a filler material. The proportion of the filler material may be selected to provide porosity for the porous material that is biocompatible, and the porous material may be shaped to provide a compliant biomedical device. In one embodiment, the compliant biomedical device is a stent such as intravascular stent. A method for fabricating a biocompatible device is also described herein. The method may include growing ceramic nanotubes on a substrate, infiltrating the ceramic nanotubes with a filler material to provide a porous material having a porosity that is biocompatible, and removing the porous material from the substrate to provide a biocompatible ceramic device. The method may also include coating the biocompatible ceramic device with a drug-eluting material.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No. 14/043,787, filed on Oct. 1, 2013, which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/708,616, filed on Oct. 1, 2012, each of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The subject matter disclosed herein relates to biocompatible devices in general and to compliant biocompatible devices in particular.

Description of the Related Art

Ceramic materials have proven to be biocompatible for a variety of applications. For example, pyrolytic carbon is a ceramic material that is currently used in several specific biomedical implant applications (including artificial heart valves), and is especially valued for its biocompatibility and resistance to blood clotting. Like most ceramics, its current indications for use are limited due to its relatively brittle nature, as well as the difficulty in producing complex geometries using traditional ceramic forming techniques. Therefore, providing a compliant ceramic device and a method of manufacture that is able to produce complex geometries would be a significant advancement in the art.

For example, stents are used for a variety of biomedical applications including coronary artery stents, peripheral artery stents, uterine stents, urethral stents, biliary stents, and stent grafts (for example as used to treat abdominal aortic aneurysm). In angioplasty applications, intravascular stents are synthetic tubes that are implanted into the vascular system to reduce the risk of restenosis (re-closing of the blood vessel) subsequent to angioplasty. As shown in FIG. 1, a balloon 110 may be inserted into an intravenous stent 120 that is in a relaxed state 120 a. The balloon 110 with the stent 120 may in turn be inserted into a vessel 130 at a point of restricted flow 140. The stent 120 may be expanded to an expanded state 120 b by inflating the balloon 110. In response to inflating the balloon 110 and expanding the stent 120, the point of restricted 140 may become less restricted. Subsequently, the balloon may be deflated and removed leaving the stent 120 within the vessel 130 in an expanded state 120 b.

Typically, the stents 120 are made of metal and coated with a drug-eluting film that elutes tissue growth inhibition drugs for approximately 2 weeks following implantation. Such stents have been shown to reduce restenosis rates from approximately 30% to less than 15%. While the reduced rates of restenosis are encouraging, even a 10% restenosis rate represents 60,000 additional surgeries in the US each year, with costs ranging from $30,000 to $100,000 each. Additionally, drug-eluting stents have also been associated with higher rates of potentially deadly thrombus formation after the drug eluting film dissipates. Thrombotic events remain the primary cause of death after angioplasty. Consequently, a stent that is more biocompatible than a metal stent would be a significant advancement in the art.

SUMMARY OF THE INVENTION

As detailed herein, a biocompatible apparatus comprises a porous material comprising a plurality of ceramic nanotubes bound together with a filler material. The proportion of the filler material may be selected to provide a porosity for the porous material that is biocompatible, and the porous material may be shaped to provide a compliant biomedical device. In one embodiment, the compliant biomedical device is a stent such as intravascular stent.

The porosity for the porous material may be selected to be biocompatible with one or more types of human tissue. In addition to having a porosity that is biocompatible, the porous material may comprise ceramic nanotubes and a filler material that are biocompatible. For example, the ceramic nanotubes may be formed of carbon and the filler material may be carbon.

A method for fabricating a biocompatible device, such as the biocompatible apparatus introduced above, is also described herein. The method may include growing a plurality of ceramic nanotubes on a substrate, infiltrating the plurality of ceramic nanotubes with a filler material to provide a porous material having a porosity that is biocompatible, and removing the porous material from the substrate to provide a biocompatible ceramic device. The method may also include coating the biocompatible ceramic device with a drug-eluting material.

The substrate may be a patterned substrate. The pattern used for the patterned substrate may be selected to provide a compliant device with a desired flexibility. In one embodiment, the substrate comprises a patterned layer of receptor material for growing the plurality of ceramic nanotubes substantially perpendicular to the substrate.

The embodiments described herein provide a variety of advantages. It should be noted that references to features, advantages, or similar language within this specification does not imply that all of the features and advantages that may be realized with the present invention should be, or are in, any single embodiment of the invention. Rather, language referring to the features and advantages is understood to mean that a specific feature, advantage, or characteristic described in connection with an embodiment is included in at least one embodiment of the present invention. Thus, discussion of the features and advantages, and similar language, throughout this specification may, but do not necessarily, refer to the same embodiment.

Furthermore, the described features, advantages, and characteristics of the invention may be combined in any suitable manner in one or more embodiments. One skilled in the relevant art will recognize that the invention may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments of the invention.

The aforementioned features and advantages of the present invention will become more fully apparent from the following description and appended claims, or may be learned by the practice of the invention as set forth hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

To enable the advantages of the invention to be readily understood, a more particular description of the invention briefly described above will be rendered by reference to specific embodiments that are illustrated in the appended drawings. Understanding that these drawings depict only typical embodiments of the invention and are not therefore to be considered to be limiting of its scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings, in which:

FIG. 1 is an illustration of a prior art intravenous stent insertion process;

FIG. 2 is a flowchart diagram of a compliant biocompatible device fabrication method;

FIG. 3 shows cross sectional illustrations depicting one embodiment of a compliant ceramic device at specific stages of one particular embodiment of the compliant ceramic device fabrication method of FIG. 2;

FIG. 4 is a top view illustration of one section of a compliant stent and various parameters associated therewith; and

FIGS. 5a and 5b are perspective view drawings depicting one embodiment of a compliant ceramic stent.

DETAILED DESCRIPTION OF THE INVENTION

Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.

FIG. 2 is a flowchart diagram of a fabrication method 200 for a compliant biocompatible device. As depicted, the method 200 includes providing 210 a patterned substrate, growing 220 ceramic nanotubes thereon, infiltrating 230 the ceramic nanotubes with a filler material, removing 240 the porous material from the patterned substrate, and coating 250 the resulting biocompatible device with a drug-eluting material. The fabrication method 200 facilitates fabricating a ceramic device that is both compliant (i.e. flexible) and biocompatible.

Providing 210 a patterned substrate may include providing a substrate made of glass, silicon, metal, or some other appropriate material, and depositing a receptor layer thereon that facilitates growing ceramic nanotubes. Alternately, the substrate may be made of a receptor material facilitates growing ceramic nanotubes. In some embodiments, a liftoff layer is deposited between the substrate and the receptor layer to facilitate subsequent removal of the ceramic nanotubes from the substrate.

The substrate and/or layers deposited thereon may be patterned by machining, photolithography, cutting, stamping, or any other method capable of producing a pattern. Patterning the substrate may include forming one or more features on the substrate, such as apertures, that improve the flexibility of the device formed thereon. Alternately, the substrate itself may remain in a substantially planar form and the patterned substrate may be provided by patterning one of more of the layers deposited on the substrate.

In one particular embodiment, the patterned substrate is provided by depositing a liftoff layer of alumina and a receptor layer of iron on a substrate of silicon, and using photolithography to etch away regions of the receptor layer where ceramic nanotube growth is not wanted.

Growing 220 ceramic nanotubes thereon may include chemical vapor deposition, arc discharge, laser ablation, or any process that facilitates ceramic nanotube growth. One of skill in the art will appreciate that the height of the nanotubes may be much greater than the pattern limits—particularly when photolithography is used to provide a patterned substrate. For example, nanotubes of greater than 500 microns in height may be grown, and pattern dimension limits of 2-3 microns may be achieved, resulting in a maximum aspect ratio of more than 200 to 1.

Infiltrating 230 the ceramic nanotubes with a filler material may include chemical vapor deposition, electroplating of metals, atomic layer deposition, dip coating with a polymer precursor or any process that deposits a filler material between the ceramic nanotubes. Infiltrating the ceramic nanotubes with a filler material may bind the ceramic nanotubes together and result in a porous material. The resulting porous material may be substantially rigid. The resulting porous material may be a ceramic or a ceramic nano-composite.

The infiltration time may control the proportion of the filler material within the porous material and the porosity of the porous material. The infiltration time and/or the proportion of the filler material may be selected to result in a porosity that is biocompatible. The ceramic nanotubes and the filler material may be made of biocompatible materials. In some embodiments, the filler material and the ceramic nanotubes are made of the same material.

Removing 240 the porous material from the patterned substrate may include conducting a liftoff process that etches away the receptor layer and/or the liftoff layer disposed between the receptor layer and the substrate. Coating 250 the resulting biocompatible device with a drug-eluting material may include depositing a drug-eluting material on the biocompatible device. In one embodiment, the drug-eluting material may be a drug-eluting polymer. One of skill in the art will appreciate that the drug-eluting material may be application dependent and may be omitted in certain applications.

FIG. 3 is a cross sectional illustration of the stages a compliant device may undergo during one embodiment of the compliant ceramic device fabrication method 200 shown in FIG. 2. Initially, at stage 300 a a substrate such as a wafer is coated with sacrificial photoresist at locations where ceramic nanotube growth is to be inhibited. At stage 300 b, a liftoff material such as alumina is deposited on the substrate followed by a receptor material such as iron at stage 300 c. For example, a 30 nm layer of alumina (Al₂O₃) could be deposited using an e-beam evaporator and a 4-10 nm layer of iron may be deposited via a thermal evaporator.

At stage 300 d, the sacrificial photoresist is etched away resulting in a patterned receptor layer on a planar substrate (referred to herein as a patterned substrate). At stage 300 e, ceramic nanotubes such as carbon nanotubes are grown on the receptor layer. The grown ceramic nanotubes may from a “forest” of nanotubes that are substantially perpendicular to the substrate. The spacing of the nanotubes may be determined by the spacing of atoms or molecules on the receptor layer. Subsequently, at stage 300 f the ceramic nanotubes are infiltrated with a filler material until a selected porosity is achieved.

For specific details of one example of the above stages and properties of compliant ceramic devices that may result therefrom, see “Material Properties of Carbon-Infiltrated Carbon Nanotube-Templated Structures for Microfabrication of Compliant Mechanisms” within Proceedings of the ASME 2011 International Mechanical Engineering Congress & Exposition, IMECE2011-64168. The authors of the aforementioned reference include at least one inventor of the present invention.

The proportion for the filler material relative to the ceramic nanotubes may be selected to provide a selected porosity for the porous material that is biocompatible. For example, the porosity of the porous material may be selected to be biocompatible with one or more types of human tissue such as vascular tissue, muscle tissue, nerve tissue, epithelial tissue, connective tissue, adenoid tissue, adipose tissue, areolar tissue, bony tissue, cancellous tissue, cartilaginous tissue, chromaffin tissue, cicatricial tissue, elastic tissue, endothelial tissue, epithelial tissue, erectile tissue, extracellular tissue, fatty tissue, fibrous tissue, gelatinous tissue, glandular tissue, granulation tissue, indifferent tissue, interstitial tissue, lymphadenoid tissue, lymphoid tissue, mesenchymal tissue, mucous tissue, myeloid tissue, osseous tissue, reticular tissue, reticulated tissue, scar tissue, sclerous tissue, skeletal tissue, subcutaneous tissue, and tissue from various organs.

One of skill in the art will appreciate that the thickness of atoms or molecules on the receptor layer as well as the infiltration time may influence the maximum strain achievable by the bulk porous material. In one embodiment, iron thicknesses of 7-10 nm and an infiltration time of approximately 30 minutes for carbon infiltrated carbon nanotubes resulted in a maximum material strain of approximately 2.3% for the bulk porous material. However, by controlling the shape of the porous material compliant devices having maximum strains of greater than 140 percent have been demonstrated for carbon infiltrated carbon nanotubes. Furthermore, controlling the shape of the porous material may result in a compliant device that performs a specific biomedical function in addition to having a desired flexibility (i.e., maximum strain). For example, compliant fluid transport devices such as stents, needles, and catheters and compliant fluid filtering devices such as artificial nephrons, blood filtration screens, or as a replacement trabecular mesh network following glaucoma surgery, may be provided. Compliant drug delivery and dispensing devices (consumable, implantable and skin attachable) and compliant meshes such as hernia meshes and bandaging meshes may also be provided.

FIG. 4 is a top view illustration of one section of a compliant stent 400 and various design parameters associated therewith. As depicted, the parameters include a strut thickness 410, a strut angle 420, a strut length 430, an end radius 440, and an end radius angle 450. The geometry of the stent 400 and the parameters associated therewith may be optimized using compliant mechanism design principles. Furthermore, computational tools such as stress analysis tools may be used to simulate the effects of changing the various parameters on the properties of the compliant stent 400. The computational tools may be provided with measurements taken on the bulk porous material provided by the method 200 or a portion thereof. The computational tools may be leveraged to optimize the compliant stent 400 or the like.

FIGS. 5a and 5b are tracings of a perspective view photo of a prototype compliant ceramic stent 500 optimized via compliant mechanism design principles and computational tools (similar to the process described above) and fabricated by the method of FIG. 2. Specifically, the depicted compliant ceramic stent 500 was formed by carbon infiltration of carbon nanotubes grown on a silicon substrate with a liftoff layer of alumina and a receptor layer of iron deposited thereon. The depicted compliant ceramic stent 500 was found to have a maximum strain of approximately 80 percent.

When rolled as suggested in FIG. 5b , the stent 500 or the like, with the testing tabs 510 removed therefrom, could be used as intravascular stent that is compressible for vascular insertion. The compressed diameter for the stent (e.g., ˜1 mm) may be less than half of an uncompressed diameter (e.g., ˜3 mm) for the stent. In one embodiment, a compressed stent 500 (or the like) is held in a compressed state via one or removable clips (not shown). The stent 500 may be coated with a drug-eluting material.

It should be noted that compliant biocompatible devices such as the stent 500 may be fabricated in a final deployed (i.e., unstressed) geometry using the methods disclosed herein. For example, while the examples depicted in the attached figures leverage planar substrates, a non-planar substrate such as a cylindrical mandrel may be used to fabricate the device stent 500 or the like.

The present invention provides compliant biocompatible devices and enables the manufacture thereof. The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope. 

What is claimed is:
 1. A biocompatible apparatus comprising: a porous material comprising a plurality of ceramic nanotubes bound together with a filler material; wherein a proportion for the filler material is selected to provide a porosity for the porous material that is biocompatible; and wherein the porous material is shaped to provide a compliant biomedical device.
 2. The apparatus of claim 1, wherein the compliant biomedical device is a stent.
 3. The apparatus of claim 2, wherein the stent is an intravascular stent.
 4. The apparatus of claim 3, wherein the stent is compressible for vascular insertion.
 5. The apparatus of claim 4, wherein a compressed diameter for the stent is less than half of an uncompressed diameter for the stent.
 6. The apparatus of claim 2, wherein the stent is coated with a drug-eluting material.
 7. The apparatus of claim 1, wherein the ceramic nanotubes and the filler material are biocompatible.
 8. The apparatus of claim 1, wherein the ceramic nanotubes and the filler material are carbon.
 9. The apparatus of claim 1, wherein the porosity for the porous material is biocompatible with vascular tissue.
 10. A method for fabricating a biocompatible device, the comprising: growing a plurality of ceramic nanotubes on a substrate; infiltrating the plurality of ceramic nanotubes with a filler material until a selected porosity is achieved to provide a porous material having a porosity that is biocompatible; removing the porous material from the substrate to provide a biocompatible ceramic device;
 11. The method of claim 10, wherein the substrate is a patterned substrate.
 12. The method of claim 11, wherein a pattern for the patterned substrate is selected to provide a compliant device.
 13. The method of claim 10, wherein the substrate comprises a patterned layer of receptor material for growing the plurality of ceramic nanotubes.
 14. The method of claim 10, wherein the plurality of ceramic nanotubes are grown substantially perpendicular to the substrate.
 15. The method of claim 10, wherein the biocompatible ceramic device is a stent.
 16. The method of claim 15, wherein the stent is a compressible intravascular stent.
 17. The method of claim 10, further comprising coating the biocompatible ceramic device with a drug-eluting material.
 18. The method of claim 10, wherein the ceramic nanotubes and the filler material are biocompatible.
 19. The method of claim 10, wherein the ceramic nanotubes and the filler material comprise carbon.
 20. The apparatus of claim 10, wherein the porosity is biocompatible with vascular tissue. 